Cellular FADD-like IL-1β-converting enzyme-inhibitory protein attenuates myocardial ischemia/reperfusion injury via suppressing apoptosis and autophagy simultaneously
| Autor: | Zhi Xing Fan, Jia Wang Ding, Di Liu, Yun Zhao Li, Jian Yang, Jing Zhang, Gang Zhou, Hui Wu, Jun Yang, Xin-An Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism Ischemia CASP8 and FADD-Like Apoptosis Regulating Protein Myocardial Infarction Medicine (miscellaneous) Autophagy-Related Proteins 030209 endocrinology & metabolism Apoptosis Myocardial Reperfusion Injury 030204 cardiovascular system & hematology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Autophagy Animals Myocytes Cardiac FADD Cells Cultured Nutrition and Dietetics biology Chemistry NF-kappa B Hypoxia (medical) medicine.disease In vitro Up-Regulation Disease Models Animal Cancer research biology.protein medicine.symptom Cardiology and Cardiovascular Medicine Apoptosis Regulatory Proteins Reperfusion injury Signal Transduction |
| Zdroj: | Nutrition, metabolism, and cardiovascular diseases : NMCD. 31(6) |
| ISSN: | 1590-3729 |
| Popis: | Background and aims Myocardial ischemia/reperfusion injury (MI/RI) is a result of coronary revascularization, and often increases cell apoptosis and autophagy. Downregulated cellular FADD-like-IL-1β-converting enzyme-inhibitory protein (cFLIP) was associated with development of several myocardial diseases, whether overexpression of cFLIP can attenuate MI/RI remains unclear. This study aimed to determine the effects of cFLIP on apoptosis and autophagy in MI/RI. Methods and results Ischemia/reperfusion (I/R) rat model and hypoxia/reoxygenation (H/R) cardiomyocytes model were established. Both I/R injury and H/R injury down-regulated expression of two cFLIP isoforms (cFLIPL and cFLIPS), and instigated apoptosis and autophagy simultaneously. Overexpression of cFLIPL and/or cFLIPS led to a significant increase in cardiomyocytes viability in vitro, and also reduced the myocardial infarct volume in vivo, these changes were associated with suppressed apoptosis and autophagy. Mechanistically, overexpression of cFLIP significantly downregulated pro-apoptotic molecules (Caspase-3, -8, -9), and pro-autophagic molecules (Beclin-1 and LC3-II). Moreover, cFLIP significantly suppressed activity of NF-κB pathway to upregulate the expression of Bcl-2, which is the molecular of interplay of apoptosis and autophagy. Conclusion Overexpression of cFLIP significantly attenuated MI/RI both in vivo and vitro via suppression of apoptosis and lethal autophagy. cFLIP can suppress activity of NF-κB pathway, and further upregulated expression of Bcl-2. |
| Databáze: | OpenAIRE |
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